We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832.... (More)

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

@article{af34bd01-4a4e-40b3-8677-3980c27e3715,
abstract = {<p>We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.</p>},
author = {Amos, Christopher I and Wang, Li-E and Lee, Jeffrey E and Gershenwald, Jeffrey E and Chen, Wei V and Fang, Shenying and Kosoy, Roman and Zhang, Mingfeng and Qureshi, Abrar A and Vattathil, Selina and Schacherer, Christopher W and Gardner, Julie M and Wang, Yuling and Bishop, D Tim and Barrett, Jennifer H and MacGregor, Stuart and Hayward, Nicholas K and Martin, Nicholas G and Duffy, David L and Mann, Graham J and Cust, Anne and Hopper, John and Brown, Kevin M and Grimm, Elizabeth A and Xu, Yaji and Han, Younghun and Jing, Kaiyan and McHugh, Caitlin and Laurie, Cathy C and Doheny, Kim F and Pugh, Elizabeth W and Seldin, Michael F and Han, Jiali and Wei, Qingyi and , and Olsson, Håkan},
issn = {0964-6906},
keyword = {Case-Control Studies,Chromosomes, Human, Pair 1,Genetic Loci,Genetic Markers,Genetic Predisposition to Disease,Genome-Wide Association Study,Guanine Nucleotide Exchange Factors,Humans,Melanoma,Meta-Analysis as Topic,Pigmentation,Polymorphism, Single Nucleotide,Skin Neoplasms},
language = {eng},
month = {12},
number = {24},
pages = {23--5012},
publisher = {Oxford University Press},
series = {Human Molecular Genetics},
title = {Genome-wide association study identifies novel loci predisposing to cutaneous melanoma},
url = {http://dx.doi.org/10.1093/hmg/ddr415},
volume = {20},
year = {2011},
}